Comparison between the gastric cancer cell line MKN-45 and the high-potential peritoneal dissemination gastric cancer cell line MKN-45P.

Peritoneal metastasis is the most common form of recurrence in gastric cancer, and is associated with a poor prognosis. It is clear that many agents are involved at the various stages of this process, however, many aspects of the progression remain unclear. In the present study we compared the gastric cancer cell line MKN-45 with the high-potential peritoneal dissemination gastric cancer cell line MKN-45P, established from MKN-45. The supernatant of culture medium of MKN-45 cells or MKN-45P cells was collected, and the concentrations of interleukin-1ß (IL-1ß), IL-6, IL-8, hepatocyte growth factor (HGF), Transforming growth factor beta-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) proteins were measured using an enzyme-linked immuno sorbent assay (ELISA) method. Invasion, wound healing and adhesion assays were performed in vitro to examine interstitial invasion, migration and adhesion in the gastric cancer cell lines. Moreover, Western blotting was performed to determine the expression of cyclooxygenase-1 (COX-1) and COX-2 proteins in the culture media of the cell lines. The concentrations of IL-6, IL-8, VEGF and MMP-2 protein in the culture supernatant of MKN-45P were significantly higher than those of MKN-45. Percent adhesion of MKN-45P was significantly higher than that of MKN-45 in the fibronectin-coated group. There was no significant difference in invasion or migration between MKN-45 and MKN-45P. COX-1 and COX-2 proteins were observed in both cell lines. These results suggested that secretion of IL-6, IL-8, VEGF and MMP-2 from cancer cells, and adhesion of cancer cells to fibronectin, were related to the establishment of peritoneal dissemination.

[Therapeutic experience of S-1 plus other drug combination therapy for synchronia multiple liver metastases of gastric cancer].

A treatment of multiple liver metastases of gastric cancer is very hard and its prognosis is extremely poor. At this time, we reviewed an efficacy of the therapeutic experience case with a new anticancer agent. The treatment was performed on nine cases of synchronia multiple liver metastases of gastric cancer since the new anticancer agent was introduced to the treatment. All of the 9 gastric cancer cases were diagnosed as being resectable other than ones with metastases to the liver, or a primary tumor resection was performed on the cases. The 1st line chemotherapy regimen was a combination of S-1+CDDP intra-arterial injection. The 2nd line chemotherapy regimen was S-1+CPT-11 intra-arterial injection. Furthermore, the 3rd line chemotherapy regimen was an administration of paclitaxel. There were no adverse events, such as hematotoxicity and non-hematotoxicity, that were greater than grade 3 during the duration of chemotherapy. Hence, we could continue the treatment regimen on all of the cases. The tumor responses for all of the cases were judged to be stable disease (SD). The best overall responses for all of the cases were judged to be progressive disease (PD). A median survival time (MST) of the treatment was 16 months, and that was significantly improved from 5.5 months, the regimen without a new anticancer agent (p=0.002). An ambulatory treatment was capable with the QOL in all of the cases. In conclusion, the tumor response did not show on the imaging, but it could be evaluable when there was an efficacy in the treatment that would support a daily life of patient.

[Conventional chemotherapy combined with the repetitive immune cell transfer for patients with refractory advanced gastric cancer].

In order to take advantage by both the anticancer effects and reconstruction of antitumor immunity, we compared the feasibility of a combination of CTL transfer and chemotherapy (ChT) for patients (pts) with malignant ascites due to carcinomatous peritonealitis of refractory gastric cancer to that of ChT only and/or cellular immunotherapy after failing ChT. A total of 22 pts, 8 underwent only conventional ChT (Group A), 6 performed cellular IT after failing ChT (Group B) and 8 underwent combination therapy (Group C), were enrolled in this retrospective study. ChT was based on conventional conditioning regimen with a standard dose for gastric cancer cases: S-1 (80-120 mg/body) plus paclitaxel (60-80 mg/m2), or CPT-11 (70-80 mg/m2) plus CDDP (80 mg/m2). Autologous tumor cells stimulated with T lymphocytes (AuTL), a kind of CTL, were generated ex vivo from peripheral blood lymphocytes over a two-week co-culturing process with autologous tumor cells separating from the ascites. IT was performed for pts of Group B and C. AuTLs were administered twice prior to ChT for pts of Group C, and were injected 1 x /2 weeks directly into the peritoneal cavity. The treatment was repeated at least three cycles with one-week interval. The mean survival period of Group A, B and C was 8.4, 5.2 and 11.3 months, respectively, and 1 pt in Group A and 3 pts in Group C survived over one year. Adverse events related to both of the ChT and AuTL transfer at all doses were minimal. Ascites had decreased or disappeared in 8 pts in this study. Lymphocytes of ascites were evaluated for cytokine production and subset of CD4+CD25+ T cell before the treatment, and after 3 treatments. The group C pts had increased IFN-gamma and IL-12 production with no TGF-beta1 responses by their ascites after 3 treatments. In contrast, the group A and B had no IFN-gamma, IL-12 or TGF-beta1 responses. These data show that combination therapy of CTL transfer and ChT is a feasible option for patients with refractory peritoneal carcinomatous of gastric cancer without serious adverse events. Although it depends on each mechanism of IT and ChT, a more stringent evaluation of CTL transfer combined with ChT for refractory gastric cancer should be performed.

The expression of p53, p21 and TGF beta 1 in gastric carcinoma.

The aim of the present study was to examine the significance of the p21 expression in gastric cancer. We examined the expression of p53, p21, TGF beta 1 and PCNA in 75 cases of gastric cancer using immunohistochemical examinations and the expression of p21 RNA by in situ hybridization (ISH). The combination of p53 and p21 expression was related to depth of invasion, lymph node metastasis, and stage grouping. The survival curves of the p53 negative-Group and the p21-positive Group were significantly higher than those of the p53-positive and the p21-negative Group, the p53-and-p21-both-positive Group, and the p53-and-p21-both-negative Group (each p < 0.01). The average PCNA Labelling Index (LI) of the p53-negative-and-p21-positive Group was significantly lower than that of either the p53-positive-and-p21-negative Group or the p53-and-p21-both-positive Group or the p53-and-p21-both-negative Group (p < 0.01, p < 0.05, p < 0.05, respectively). All of the p53-and-p21-both-positive cases were TGF beta 1 positive, and the rate of the TGF beta 1 positive cases in the p53-and-p21-both-positive Group was significantly higher than that of the p53-positive-and-p21-negative Group, and than the rate in the p53-and-p21-both-negative Group (each p < 0.01). The survival curves of the cases with expression of p21 RNA were higher than that of cases without p21 RNA (p < 0.05). Many of the p53-positive-and-p21-negative cases were advanced cancer with very poor prognosis, but many of the p53-negative-and-p21-positive cases were early cancer with good prognosis. These results suggest that p21 suppressed synthesis of DNA via PCNA, and TGF beta 1 is a regulation factor for the expression of p21, and that the combination of p53 and p21 expression is concluded to be a useful prognostic marker of gastric carcinoma.

A case of small mucosal gastric carcinoma with lymph node metastasis: a case report.

We have experienced a case of small early mucosal gastric cancer with lymph node metastasis. The patient was a 75-year-old woman diagnosed as having early gastric cancer type 0 IIa on the greater curvature of the antrum. We performed distal gastrectomy, with Billroth I method reconstruction. The tumor lesion was on the greater curvature of the antrum. Metastasis was discovered in the number 4d lymph node, histologically. The tumor was type 0 IIa confined to the mucosa, 1.0 cm in diameter and differentiated histological type, and no ulcer scar could be seen in tumor lesion. However, the tumor was massively invading to the mucosal membrane, with positive lymph vessel invasion, and was of mixed histological type. This was a rare case of small early mucosal cancer 1.0 cm in diameter with lymph node metastasis.

Two cases of early gastric carcinoma with synchronous liver metastasis.

We have experienced two cases of early gastric cancer with synchronous liver metastasis. One patient was a 64-year-old man diagnosed as having early gastric cancer type 0 IIa at 15 x 10 mm on the lesser curvature of the cardia. The other patient was a 58-year-old man diagnosed as having early gastric cancer type 0 IIa + IIc at 24 x 18 mm on the posterior wall of the antrum. The histological findings showed that proliferation of moderately differentiated tubular adenocarcinoma with hepatoid pattern was massively invading to the deep layer of the submucosa, with positive lymph vessel, vein invasion and lymph node metastasis, in both cases. These results suggested that elevated or mixed macroscopic type, differentiated adenocarcinoma massively invading to the deep layer of submucosa, positive lymph vessel and vein invasion, lymph node metastasis, and hepatoid adenocarcinoma were risk factors for liver metastasis from early gastric cancer.

Alpha-fetoprotein-producing early gastric cancer: report of two cases.

We have experienced two cases of alpha-fetoprotein (AFP)-producing early gastric cancer. One patient was a 73-year-old man diagnosed as having an early gastric cancer type 0 I + IIa at 40 x 40 mm on the greater curvature of the lower body of the stomach. The histological findings showed that proliferation of a well-differentiated tubular adenocarcinoma with hepatoid pattern was massively invading to the middle layer of the submucosa, with positive lymph vessel, and lymph node metastasis. The other patient was a 76-year-old man diagnosed as having an early gastric cancer type 0 IIa + IIc at 25 x 25 mm on the anterior wall on the greater curvature of the antrum. The histological findings showed that proliferation of a small cell carcinoma was massively invading to the deep layer of the submucosa, with positive lymph vessel, and lymph node metastasis. AFP was immunohistochemically found in the tumor cells of these two cases. Both patients died from liver metastasis. AFP-producing early gastric cancer was concluded to be at high risk of liver metastasis.

Early gastric carcinoma associated with amyloidosis: a case report.

We have experienced a case of early gastric carcinoma associated with amyloidosis. The patient was a 63-year-old woman diagnosed as having early gastric cancer type 0 Ila at the anterior wall on the greater curvature of the antrum, and multiple polypoid lesions on the antrum to the body of the stomach. We performed total gastrectomy, and rho-Roux-en-Y reconstruction. The tumor lesion was recognized at the anterior wall of the prepylorus, and the multiple polypoid lesions which were composed of amyloid masses were recognized on the whole stomach. The histological findings of the biopsy specimens from the rectum and the skin showed no amyloid-deposit. The urine examination was negative for a Bence-Jones protein reaction. This was a rare case of early gastric carcinoma associated with stomach amyloidosis, apparently confined to the stomach.

A long-term survival case of gastric cancer treated by continuous low-dosage 5-fluorouracil and cisplatin: a case report.

We have experienced a case of long-term survival after treatment with low dosage 5-fluorouracil (5-FU) and cisplatin (FP regimen). The patient was a 60-year-old man diagnosed as having advanced gastric cancer type 3 with numerous large lymph node metastases. After treatment with 2 courses of FP regimen, the primary tumor and para-aortic lymph nodes were decreased in size by 41% and 92%, respectively, and the serum level of alpha-fetoprotein was decreased to normal. We then recommended surgery, but the patient did not consent. Therefore, he was treated with a third course of FP regimen. He died at 3 years later. These results suggested that the FP regimen was an effective treatment for advanced gastric cancer which was difficult for curative resection because of the numerous large lymph node metastases.